BackgroundSeveral observational cohort and meta-analytical studies in humans have shown that statin users have a lower risk of fractures or greater bone mineral densities (BMD) than nonusers. However, some studies including randomized clinical trials have the opposite results, particularly in Asian populations.ObjectiveThis study investigates the impacts of statins on new-onset osteoporosis in Taiwan.MethodsIn a nationwide retrospective population-based cohort study, 45,342 subjects aged between 50–90 years having received statin therapy (statin-users) since January 1 2001, and observed through December 31 2013 were selected from the National Health Insurance Research Database of Taiwan. Likewise, 115,594 patients had no statin therapy (statin-non-users) were included as controls in this study. Multivariable Cox proportional hazards analysis for drug exposures was employed to evaluate the association between statin treatment and new-onset of osteoporosis risk. We also used the long-rank test to evaluate the difference of probability of osteoporosis-free survival.ResultsDuring the 13-year follow-up period, 16,146 of all enrolled subjects (10.03%) developed osteoporosis, including 3097 statin-users (6.83%) and 13,049 statin-non-users (11.29%). Overall, statin therapy reduced the risk of new-onset osteoporosis by 48% (adjusted hazard ratio [HR] 0.52; 95% CI 0.50 to 0.54). A dose-response relationship between statin treatment and the risk of new-onset osteoporosis was observed. The adjusted hazard ratios for new-onset osteoporosis were 0.84 (95% CI, 0.78 to 0.90), 0.56 (95% CI, 0.52 to 0.60) and 0.23 (95% CI, 0.21 to 0.25) when cumulative defined daily doses (cDDDs) ranged from 28 to 90, 91 to 365, and more than 365, respectively, relative to nonusers. Otherwise, high-potency statins (rosuvastatin and atorvastatin) and moderate-potency statin (simvastatin) seemed to have a potential protective effect for osteoporosis.ConclusionsIn this population-based cohort study, we found that statin use is associated with a decreased risk of osteoporosis in both genders. The osteoprotective effect of statins seemed to be more prominent with a dependency on the cumulative dosage and statin intensity.

BackgroundStatins have been linked to new-onset osteoporotic fractures (NOFs), and different statins may alter the risk for the development of NOFs.AimIn this study, we investigated the association between different statins and the development of NOFs.Patients and methodsThis was a longitudinal cohort study performed using data from claim forms submitted to the Taiwan Bureau of National Health Insurance, including case patients with NOFs from January 2004 to December 2013 and non-NOF subjects. We estimated the hazard ratios (HRs) of NOFs associated with statin use. Nonuser subjects served as the reference group.ResultsA total of 44,405 patients with NOFs were identified from among 170,533 patients with hyperlipidemia during the study period. The risk of developing NOFs after adjusting for age, sex, comorbidities, and concurrent medication use was lower among users of atorvastatin (HR, 0.77; 95% CI, 0.71–0.84) and rosuvastatin (HR, 0.72; 95% CI, 0.64–0.81) than among simvastatin users. Lovastatin, pravastatin, fluvastatin, and pitavastatin were not associated with the risk of developing NOFs compared with simvastatin users.ConclusionThis study supports previous reports regarding a beneficial effect of statin use and NOF risk, but not all statins. Patients taking atorvastatin or rosuvastatin were at lower risk of developing NOFs compared with simvastatin users during the 10-year follow-up. Other statins such as pravastatin, fluvastatin, lovastatin, and pitavastatin were not associated with NOFs. This study also highlighted that high-potency statin has a dose–response effect on lower NOF risk.

Recent studies have demonstrated that the plasma soluble receptor for advanced glycation end-products (sRAGE) play a major role in developing macrovascular complications of type 2 diabetes, including peripheral arterial occlusion disease (PAOD). Cilostazol is an antiplatelet, antithrombotic agent, which has been used for the treatment of PAOD. We hypothesized that cilostazol attenuates the severity of PAOD in patients with type 2 diabetes through the augmentation of plasma sRAGE. Ninety type 2 diabetic patients with PAOD defined as intermittent claudication with ankle-brachial index (ABI) ≦0.9 were recruited for an open-labeled, placebo-controlled study for 52 weeks with oral cilostazol 100 mg twice daily (n = 45) or placebo (n = 45). Fasting plasma sRAGE, endothelial variables of E-selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1), and inflammatory markers of high-sensitivity C-reactive protein (hsCRP) and tumor necrosis factor-α (TNF-α) were determined. After completely the 52-week treatment program, the ABI values were elevated in cilostazol group (P < 0.001). The plasma sRAGE was significantly increased (P = 0.007), and hsCRP, sVCAM, and E-selectin concentrations were significantly decreased (P = 0.028, <0.001 and <0.001, respectively) with cilostazol treatment. In a partial correlation analysis with adjustments for sex and age, the net change of sRAGE significantly correlated with the change of ABI in the cilostazol group (P = 0.043). In a stepwise multiple regression model, only the change with regards to sRAGE was significantly associated with the change of ABI (P = 0.046). Our results suggest that cilostazol may effectively attenuate the severity of PAOD in patients with type 2 diabetes. Plasma sRAGE plays a role as an independent predictor for improving the index of PAOD.

PurposeHemophilia A and B (HA, HB) are the most common X-linked inherited bleeding disorders. The introduction of factor concentrates has allowed for control of the lifelong chronic disease. However, no studies have been published regarding the epidemiology of hemophilia in Taiwan. Our aim was to determine the prevalence, incidence, and mortality rate, as well as trends in the use of factor concentrates, in individuals with hemophilia in Taiwan.Materials and MethodsA retrospective study was conducted using the National Health Insurance Research Database between 1997 and 2007.ResultsWe identified 988 males with hemophilia (HA : HB ratio=5.4 : 1). The mean prevalence per 100000 males was 6.7±0.1 for HA and 1.2±0.1 for HB. The estimated mean annual incidence per live male birth was 1 in 10752 for HA and 1 in 47619 for HB. Standardized mortality ratios for males with hemophilia (all severities) or severe hemophilia were 1.3- and 2.1-fold higher than that of the general male population, respectively. Mean factor VIII (FVIII) and factor IX (FIX) usage was 1.5003±0.4029 and 0.3126±0.0904 international units (IUs) per capita, respectively. Mean FVIII and FIX usage per patient with hemophilia (all severities) or severe hemophilia was 44027±11532 and 72341±17298, respectively, and 49407±13015 and 74369±18411 IUs per person with HA or HB, respectively.ConclusionOur data revealed epidemiologic and factor concentrate usage trends in males with hemophilia in Taiwan, highlighting a need for improvements in the mandatory National Health Insurance registry. A better-designed, patient-centered registry system would enable more detailed patient information collection and analysis, improving subsequent care.

The unpredictable course followed by severe, chronic, non-healing wounds not only restricts the daily activities of affected patients, but also impairs their quality of life (QOL). Hyperbaric oxygen therapy (HBOT) treatment for such wounds elevates tissue oxygen content, increases cellular repair functions and the probability of wound healing, and improves the patient's QOL. This was a longitudinal, prospective study, and used a purposive sampling method. A total of 15 patients receiving HBOT at a medical center were enrolled. Data were collected by questionnaire before and after HBOT. The questionnaire included basic patient characteristics, self-perceived wound severity, wound physiological indices, and a QOL scale. The overall QOL score of the subjects after HBOT was higher than before HBOT. After HBOT, there was a positive correlation between the QOL of patients with problem wounds and the scoring of the Strauss wound classification system. After HBOT, there was a negative correlation between the QOL of patients with problem wounds and their self-perceived severity of the wound. The results were then used to provide suggestions for nursing care and additional research directions in order to effectively assist patients with problem wounds receiving HBOT, with the goal of achieving an optimal QOL.

Correspondence on 'Impact of rheumatoid arthritis on major cardiovascular events in patients with and without coronary artery disease' Globally, coronary artery disease (CAD) is one of the leading causes of mortality in patients with rheumatoid arthritis (RA). 1 2 The major pathological changes in RA-associated CAD are high rate of unstable coronary plaque and increased local inflammation, as inferred from autopsy reports. 3 Recently, Løgstrup et al 4 reported that RA was significantly associated with a 10-year risk of myocardial infarction, major adverse cardiovascular events and all-cause mortality regardless of the presence of CAD in patients undergoing coronary angiography (CAG). While the patients with RA associated CAD carry the largest risk, the additive risk of RA in patients without CAD is minor. These findings were published in the September 2020 issue of the Annals of the Rheumatic Diseases. Certainly, the findings of Løgstrup et al hold significance for clinicians; however, four points remain unaddressed, and we wish to communicate these to the authors. First, low-density lipoprotein cholesterol (LDL-C) plays a vital role in the perpetuation and pathogenesis of CAD. 5 The elevated level of LDL-C is a strong independent predictor of cardiovascular events, and lowering the LDL-C to <70 mg/ dL has proved to be effective in the primary and secondary prevention of CAD. 5-7 In recent reports, it has been stated that emphasising the importance of optimal LDL-C control early in life at a younger age. 8 However, the LDL level was not described in the baseline characteristics of these four groups. Therefore, the conclusions may not be rigorous without considering these vital factors. Second, several previous clinical trials in patients with CAD have demonstrated that high-intensity statin therapy significantly reduces cardiovascular events when compared with moderate-intensity statin therapy. 9-12 Furthermore, it has been established that higher-dose statin therapy was associated with a lower risk for cardiovascular events than moderate-dose statin therapy in patients with CAD. 13 However, the percentages of patients using statin were not comparable and the type and dosage of statin were not described in the baseline characteristics of these four groups. These issues might have nullified some of the results related to this study. Third, despite the higher risk for cardiovascular events, treatment compliance was poor in patients with RA because these patients are given many oral drugs. 14 In this situation, the comparison between those with and without CAD among the patients with RA may be influenced by treatment compliance. In particular, there was a low rate of compliance in long-term (over 10 years) follow-up. Thus, treatment compliance rates for patients with RA were probably suboptimal in this study and hence may act as a confounding variable. Finally, during the baseline participation in this study, only patients undergoing CAG were recruited, and the decision was made by the physician to either perform CA...

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Several studies have shown that statin users have a lower risk of new-onset dementia (NOD) compared nonusers. However, other studies have shown opposite results. In this study, we investigated the association between the use of statins and the development of NOD. This was a longitudinal cohort study using data from claim forms submitted to the Taiwanese Bureau of National Health Insurance. The study included patients with NOD and non-NOD subjects from January 2002 to December 2013. We estimated the hazard ratios (HRs) of NOD associated with statin use, whereas nonuser subjects were used as a reference group. A total of 19,522 NOD cases were identified in 100,610 hyperlipidemic patients during the study period. The risk of NOD, after adjusting for sex, age, comorbidities, and concurrent medication, was lower among statin users than nonusers (HR 0.95, 95% CI [confidence interval] 0.94–0.96; P < .001). The adjusted HRs for NOD were 1.53 (95% CI, 1.45–1.62), 0.63 (95% CI, 0.57–0.71), and 0.34 (95% CI, 0.30–0.38) when the cumulative defined daily doses ranged from 28 to 365, 366 to 730, and more than 730 relative to nonusers, respectively. We concluded that statin use is associated with a decreased NOD risk. The protective effect of statins for NOD seemed to be related to high exposure to statins. This study also highlights that high exposure to statins has a dose-response effect on lowering NOD risk.